Date on Master's Thesis/Doctoral Dissertation

5-2020

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Interdisciplinary and Graduate Studies

Degree Program

Interdisciplinary Studies with a specialization in Translational Neuroscience, PhD

Committee Chair

Depue, Brendan

Committee Co-Chair (if applicable)

Lyle, Keith

Committee Member

Lyle, Keith

Committee Member

Newton, Tamara

Committee Member

Brueckner-Collins, Jennifer

Committee Member

Fernandez-Botran, Rafael

Author's Keywords

anxity; nucleus; stria termilas

Abstract

Anxiety disorders afflict up to one third of the population. Research to date has primarily focused on the amygdala, however, new perspectives suggest that a tiny basal forebrain region known as the bed nucleus of the stria terminalis (BNST) may hold key insights into understanding and treating anxiety disorders. Therefore, my first aim was to empirically investigate the importance and influence of the BNST in anxiety processing. Using fearful faces and human screams as aversive stimuli, two threat conditions were created: one in which threats were certain and predictable (fear) and another in which threats were uncertain and unpredictable (anxiety). Results indicated that the amygdala showed preferential engagement during fear and displayed functional connectivity with regions involved in stimulus processing and motor response. By contrast, the BNST preferentially responded during anxiety and exhibited functional connectivity with prefrontal regions underlying interoception and rumination. Together, this suggests that the amygdala and BNST play distinct but complementary roles during threat processing, with the BNST specializing in the detection of potential threats to promote hypervigilant monitoring. A primary mechanism of impaired functioning in anxiety disorders is emotion dysregulation, and has been another key focus in research. However, most emotion regulation (ER) paradigms use explicitly cued pictorial stimuli (negative scenes or faces) that induce disgust, when anxiety, by definition, is a sustained response to uncertain or unpredictable prospective threats. Therefore, my second aim was to specifically investigate anxiety regulation. 30 participants underwent high-resolution fMRI (1.5 mm3) while performing a novel task — a hybrid of the previous task and a canonical ER task – in order to: 1) investigate whether the BNST can be downregulated during uncertain anticipation, and 2) characterize the prefrontal regulatory mechanisms. Results showed that anxiety regulation was associated with pronounced BNST downregulation, enhanced activation of prefrontal regions (right middle frontal gyrus [rMFG], right inferior frontal gyrus [rIFG]), and increased connectivity between the rIFG and BNST while simultaneously decreasing connectivity among attentional circuits. These results provide the first evidence that the BNST can be volitionally downregulated and further suggest that anxiety regulation modulates higher-order attentional systems to putatively reduce vigilance.

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